Nonviral mRNA delivery for retinal gene therapy

Gene therapy holds significant promise for treating genetic diseases. Ophthalmology has been at the forefront of this innovation, with one ocular gene therapy already approved by the FDA and EMA. However, challenges such as high costs, immune responses, and potential long-term toxicity of viral vectors remain major barriers to clinical translation.
Our lab is committed to overcoming these limitations by combining in vitro transcribed mRNA and nonviral delivery systems to target inherited retinal diseases (IRDs). As highlighted in our opinion article in Trends in Molecular Medicine (DOI: 10.1016/j.molmed.2023.11.009), it is essential to develop novel approaches that not only match the efficacy of viral gene therapies but also prioritize safety and accessibility. By leveraging advancements in nanotechnology and mRNA therapeutics, we aim to make retinal gene therapies safer and more widely available, particularly in low- and middle-income countries.
Since 2022, we have been testing lipid nanoparticle-mediated delivery of synthetic mRNA for retinal gene supplementation in cellular and mouse models of Choroideremia. We are assessing toxicity, transfection efficiency, durability of expression, and retinal biodistribution. Once optimized, we plan to tailor the mRNA cargo to deliver genome editing tools, establishing a versatile platform to address a wide range of hereditary retinopathies.